The analysis of volatile organic compounds in exhaled breath and biomarkers in exhaled breath condensate in children – clinical tools or scientific toys?

Abstract

Current monitoring strategies for respiratory diseases are mainly based on clinical features, lung function and imaging. As airway inflammation is the hallmark of many respiratory diseases in childhood, noninvasive methods to assess the presence and severity of airway inflammation might be helpful in both diagnosing and monitoring paediatric respiratory diseases. At present, the measurement of fractional exhaled nitric oxide is the only noninvasive method available to assess eosinophilic airway inflammation in clinical practice. We aimed to evaluate whether the analysis of volatile organic compounds (VOCs) in exhaled breath (EB) and biomarkers in exhaled breath condensate (EBC) is helpful in diagnosing and monitoring respiratory diseases in children. An extensive literature search was conducted in Medline, Embase and PubMed on the analysis and applications of VOCs in EB and EBC in children. We retrieved 1165 papers, of which nine contained original data on VOCs in EB and 84 on biomarkers in EBC. These were included in this review. We give an overview of the clinical applications in childhood and summarize the methodological issues. Several VOCs in EB and biomarkers in EBC have the potential to distinguish patients from healthy controls and to monitor treatment responses. Lack of standardization of collection methods and analysis techniques hampers the introduction in clinical practice. The measurement of metabolomic profiles may have important advantages over detecting single markers. There is a lack of longitudinal studies and external validation to reveal whether EB and EBC analysis have added value in the diagnostic process and follow-up of children with respiratory diseases. In conclusion, the use of VOCs in EB and biomarkers in EBC as markers of inflammatory airway diseases in children is still a research tool and not validated for clinical use.

Childhood asthma biomarkers: present knowledge and future steps

“…For the time being, FE NO is the only validated non-invasive method for assessing asthmarelated eosinophilic inflammation in clinical practice [65], but it has various shortcomings and would need to be adopted in combination with other useful markers.…”

“…Two pediatric studies found significantly higher mean levels of nitrite/nitrate [63,64] in asthmatic children than in healthy controls, but there have been conflicting results regarding the association between these molecules and asthma severity [13,65]. Nitrite/nitrate also does not seem able to predict the failure of ICS tapering, nor does it correlate with symptoms, lung function, or FE NO [65]. The 3-nitrotyrosine content in EBC, deriving from the nitrosylation of the tyrosine residues in proteins, was examined in two pediatric studies, with mixed results [66,67].…”

“…But a single marker can hardly be expected to reflect and monitor such complex and heterogeneous pathological processes as those involved in asthma, because too many cellular and molecular mechanisms are implicated, interacting in complex networks [65]. The profiles of several biomarkers may better reflect different pathogenic mechanisms and disease phenotypes [ Figure 1].…”

“…The VOCs in EB probably result from the breakdown of larger molecules, and originate both from the lungs and upper airways, and from the blood circulation. Although VOC collection is affected by several environmental, physiological and methodological factors, the concentrations of different compounds is strongly influenced by the presence of airway inflammation [2,65]. VOCs in EB can be investigated using various techniques, the most often used being gas chromatography coupled with mass spectrometry (GC-MS) or flame ionization detection (GC-FID) [99].…”

“…The reported results nevertheless need to undergo external validation, and further research must be done on how disease severity and treatment affect the pattern of metabolites identified using these techniques. Their practical role in asthma monitoring still remains to be seen [65].…”